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Management of diabetic foot remains a major challenge for healthcare system. Though wound healing is a multiphase process and involved multiple biomarkers that acts in stepwise manner, pathophysiology diabetic foot ulcers is still not much clear and need standardization. Matrix metalloproteinases (MMPs) are often linked with non-healing characteristic of diabetic foot ulcers. They play vital roles in various phases of healing process. Major functions are removal of damaged extracellular matrix in inflammatory phase, breakdown of capillary basement membrane prior to angiogenesis and facilitation in fibroblast migration during proliferation phase. For efficient healing, these enzymes are needed in certain amount only. Imbalance of these enzymes leads to excessive degradation which has been linked with the non-healing nature of diabetic ulcers. This chapter will shed light on the role of MMP’s in various phases of wound healing and the inhibitors of MMP’s from natural as well as synthetic origin. It would help researchers and physicians to the understand nature of diabetic foot more clearly and design of strategies for diabetic foot management.

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